The proposed research is concerned with the application of techniques for high resolution electron microscopy associated with cytochemical and immunochemical methods to pathogenic fungi. Selected strains of Cryptococcus neoformans, Histoplasma capsulatum, Blastomyces dermatitidis, Torulopsis glabrata, Candida spp. and Aspergillus fumigatus will be used. Objectives are: (1) Visualization of macromolecular structures and morphological variations of cellular components during physiological processes such as cell division (budding, septation); characteristics and variation in quantity of ribosomes, glycogen particles, lipid droplets, as well as cellular organelles (e.g., mitochondria), during transition from yeast to hyphal growth and vice versa. (2) Morphogenic observations on dormant and germinating spores, particularly conidia of A. fumigatus, chlamydospores of C. albicans, and tuberculate spores of H. capsulatum. (3) Localization of fungal antigens, e.g., protein and carbohydrates in cell walls and cell membranes of C. albicans and C. neoformans, employing ferritin conjugates and usual immunological methods. (4) Comparison between the in vitro and in vivo results to learn about significant ultrastructural changes undergone by fungi from saprophytic to parasitic conditions (e.g., changes from mycelium to yeast growth in dimorphic fungi). (5) Characterization of host-fungus interrelationships, phagocytosis, and lysosomal enzymes. (6) Search for evolutionary trends among the selected organisms, many of which are ranked in doubtful taxonomic positions (e.g., Torulopsis in the Cryptococcaceae). The project is concerned with the relationship of form to function at the molecular level. It concentrates on organisms of significance in disease. The project will also provide basic information on evolution from lower to higher forms of life, since fungi occupy an important phylogenetic position as lower eucaryotes.